The central nervous system may be involved in TCDD toxicity

In the present study, 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) was administered to both the most TCDD-susceptible (Long-Evans) and the most TCDD-resistant rat strain (Han/Wistar) as a constant 1-week infusion either centrally (intracerebroventricularly; i.c.v.) or peripherally (s.c.). Lethality, feed and water consumption as well as weight gain were observed. For both strains of rat, feed intake was most severely affected in the groups given TCDD i.c.v., while the s.c. infusion of TCDD did not markedly depress eating. The same pattern of responsiveness was discernible in the reduction of water consumption and of weight gain. Two out of 7 i.c.v.-treated rats of the TCDD-susceptible strain died after TCDD exposure, whereas all s.c.-dosed animals survived. A statistically significant strain difference was manifest in the magnitude of response between the i.c.v.-TCDD groups in feed intake and body weight change. Moreover, no deaths occured among the TCDD-resistant Han/Wistar rats. An additional experiment did not disclose any difference in TCDD toxicity between 2 peripheral routes (s.c. and i.p.). Further, lethality tended to have a shorter latent period with the readily absorbable dimethyl sulphoxide (DMSO) as the solvent than with the potentially slowly absorbed corn oil. These findings suggest an important role for the central nervous system in TCDD toxicity.